CLINICAL TRIALS AND
NATURAL HISTORY STUDY
Vikram Shakkottai, MD, PhD
University of Michigan
Ataxia trials

82 listed studies on www.clinicaltrials.gov
Phase I
Small group (20-100). Assess the safety,
tolerability, pharmacokinetics, and
pharmacodynamics of a drug
Phase II
Larger group (20-300). Designed to assess
efficacy, as well as to continue Phase I
safety assessments
Phase III
Randomized controlled multicenter trials on
larger groups (300–3,000). Aimed at
being the definitive assessment of how
effective the drug is, in comparison with
current 'gold standard' treatment.
Sporadic ataxia
Study
Aim
Location
PI
Results
Riluzole
Phase II
S. Andrea
Hospital
(Italy)
Giovanni Ristori
Riluzole reduces ICARS
score by > 5 points
Coenzyme
Q10
Phase I
UT Galveston
UF
H Subramony
Completed/ Unpublished
Rifampicin
(MSA)
Phase III
Multi-center
Phillip Low
David Robertson
Sid Gilman
Not yet recruiting
Lithium
(MSA)
Phase II
University
Federico II
(Italy)
Alessandro Filla
Ongoing
Friedreich Ataxia
Study

Aim
20 studies
Location
PI
Results
Idebenone
Phase III
UCLA
CHOP
Susan Perlman
David Lynch
No significant alteration in
neurological function at 6months (Arch Neurol. 2010
67:941-7)
Deferiprone
Phase II
Belgium
France
Italy
Spain
Massimo Pandolfo
Arnold Munnich
Franco Taroni
Javier Arpa
Completed/ Unpublished
Epoetin alfa
Phase II
Federico II
University
(Italy)
Alessandro Filla
Ongoing
Carbamylated
Erythropoietin
Phase II
Austria
Germany
Italy
H. Lundbeck A/S
(company)
Ongoing
Dominant ataxias
Study
Aim
Location
PI
Results
Lithium
(SCA1)
Phase I
NIH
Riluzole
Phase
II/III
S. Andrea
Hospital
Silvia Romano
Ongoing
Varenicline
(SCA3)
Phase II
USF
UCLA
Theresa Zesiewicz
Ongoing
Completed/ Unpublished
Riluzole in ataxia




In a randomized, double-blind, placebo-controlled pilot
trial, 40 patients presenting with cerebellar ataxias of
different etiologies were randomly assigned to riluzole (100
mg/day) or placebo for 8 weeks.
Outcome measure: 5 points in the International Cooperative
Ataxia Rating Scale (ICARS).
The number of patients with a 5-point ICARS drop was
significantly higher in the riluzole group than in the placebo
group after 8 weeks (13/19 vs 1/19). The mean change in
the riluzole group ICARS after treatment revealed a
decrease (p < 0.001) in the total score -7.05 vs 0.16.
Sporadic, mild adverse events occurred.
Ristori et. Al., Neurology. 2010;74:839-45.
Riluzole in ataxia
Ristori et. Al., Neurology. 2010;74:839-45.
Natural History Study of and Genetic
Modifiers in Spinocerebellar Ataxias


To establish a new multidisciplinary consortium that
provides the infrastructure for future clinical trials to
test safety and efficacy of therapeutic interventions
for spinocerebellar ataxias.
Rare Disease = # of Patient <200,000 in US
Participating Sites of SCA-CRC
Original Sites (
)

University of Florida: Ashizawa, Subramony

UCLA: Perlman

University of Chicago: Gomez

Emory University: Wilmot

University of Michigan: Paulson

University of Minnesota: Bushara

University of South Florida: Zesiewicz

University of Utah: Pulst
Voluntary Participants (
)

Johns Hopkins University: Ying

Harvard University: Schmarmann

UCSF: Kang

Columbia University: Kuo/Fahn

NIH, NINDS: Galpern, ORDR: Ferguson

EuroSCA, Brazil, Japan
Patient Support Organizations

National Ataxia Foundation: S. Hagan

Sparkman Fund
Specific Aims of SCA-CRC




Aim 1. Establish the organizational foundations for the CRCSCA
Aim 2. Recruit patients, obtain longitudinal clinical data for
future clinical trials, and develop novel methods for clinical
trials for a small sample size.
Aim 3. Initiate a pilot study to determine genetic modifiers of
SCA 1, 2, 3 and 6
Aim 4. Establish a training program for cultivating physicianscientist investigators for clinical and translational research of
SCA
Current enrollment
SARA
Type of SCA
N
Mean age ± SD
Age range
Age at onset
SCA1
30
48.68 ± 13.2
1-65
47.68
14.87
SCA2
31
50.06 ± 12.04
26-71
49.06
15.81
SCA3
64
51.6 ± 12.63
1-74
50.93
17.03
SCA6
45
62.9 ± 14.71
1-91
61.95
15.26
Total
170
53.8 ± 14.1
1-91
52.91
15.97
Future directions
Spin-off clinical trials:




Varenicline for SCA3
Lithium for SCA1
CoQ10 for SAOA
Riluzole for SCAs
Acknowledgements





Tetsuo Ashizawa
H. Subramony
National Ataxia Foundation
NIH 5RC1NS068897 (PI Ashizawa)
Training component of the NIH 5RC1NS068897